1. Field of the Invention
The invention is directed to crystalline forms of a 3-carboxypropyl-aminotetralin compound which are useful as mu opioid receptor antagonists. The invention is also directed to pharmaceutical compositions comprising such crystalline compounds, methods of using such compounds for treating or ameliorating medical conditions mediated by mu opioid receptor activity, and processes useful for preparing such compounds.
2. State of the Art
Mu opioid receptor antagonists are expected to be useful for treating or ameliorating medical conditions mediated by mu opioid receptor activity. In particular, peripherally selective mu opioid receptor antagonists are expected to be useful for treating conditions such as opioid-induced bowel dysfunction and postoperative ileus. Commonly-assigned U.S. Provisional Application Nos. 61/007,220, filed Dec. 11, 2007, and 61/049,219, filed Apr. 30, 2008 and U.S. application Ser. No. 12/331,659, filed Dec. 10, 2008, disclose 3-carboxypropyl-aminotetralin compounds. In particular, the compound (S)-4-((2S,3S)-7-carbamoyl-1,1-diethyl-3-methoxy-1,2,3,4-tetrahydronaphthalen-2-ylamino)-2-cyclohexylmethyl-butyric acid (compound 1):
is specifically disclosed in these applications as demonstrating mu opioid receptor antagonist activity.
To effectively use this compound as a therapeutic agent, it would be desirable to have a solid-state form that can be readily manufactured and that has acceptable chemical and physical stability. For example, it would be highly desirable to have a physical form that is thermally stable, for example at temperatures exceeding about 160° C. or about 180° C., and is not deliquescent, thereby facilitating processing and storage of the material. Crystalline solids are generally preferred over amorphous forms, for enhancing purity and stability of the manufactured product.
No crystalline forms of compound 1 have previously been reported. Accordingly, a need exists for a stable, crystalline form of compound 1 that is not deliquescent, and exhibits favorable thermal stability.